Process for the synthesis of 4-(2-pyridylamido ethyl) piperidines

Claim 2

A process for preparing a 4-(2-pyridylamidoethyl)piperidine of the structure ##EQU5## wherein R is selected from the group consisting of 3-(2-methoxy) pyridyl, 3-(2-ethoxy)pyridyl and 2-(4-chloro)pyridyl comprising contacting the corresponding 4-(2-pyridylamidoethyl)pyridine in reaction-inert solvent with hydrogen at about 25 to 75 psig. and about 15° to 40°C. in the presence of noble metal catalyst and a substantially equimolar portion of acid until reaction is substantially complete.

Claim 3

The process of claim 1 wherein R is 3-(2-methoxy) pyridyl.

Claim 4

The process of claim 1 wherein said acid is hydrochloric acid.

Claim 5

The process of claim 1 wherein said acid is sulfuric acid.

Claim 6

The process of claim 1 wherein said solvent is lower alkanol.

Claim 7

The process of claim 5 wherein said solvent is methanol.

Claim 8

The process of claim 1 wherein said catalyst is platinum oxide.

Claim 9

A process for preparing a 4-(2-pyridylamidoethyl)piperidine of the structure ##EQU6## wherein R is selected from the group consisting of 3-(2-methoxy) pyridyl, 3-(2-ethoxy)pyridyl and 2-(4-chloro)pyridyl comprising contacting the corresponding 4-(2-pyridylamidoethyl)pyridine with a substantially equimolar portion of an agent chosen from the group consisting of benzyl bromide, benzyl iodide, the α-bromo- and α-iodoxylyenes, the α-bromo- and α-iodomethylnaphthalenes and the mono- and disubstituted derivaties thereof wherein said substituents are chosen from the group consisting of lower alkyl, lower alkoxy, phenyl and phenoxy, in reaction-inert solvent at reflux temperature until reaction to form the corresponding N-substituted-4-(2-pyridylamidoethyl)pyridinium salt is substantially complete; contacting said salt with metal hydride selected from the group consisting of sodium borohydride, lithium aluminum hydride and sodium bis-(2-methoxyethoxy)aluminum hydride in reaction-inert solvent until reaction to form the corresponding N-substituted-4-(2-pyridylamidoethyl)-1,2,5,6-tetrahydropyridine is substantially complete; and contacting said tetrahydropyridine with hydrogen at up to about 400 psig. from about 40° to 75°C. in reaction-inert solvent in the presence of moble metal catalyst and an approximately equimolar portion of acid until reaction to form the corresponding 4-(2-pyridylamidoethyl)piperidine is substantially complete.

Claim 10

A process for preparing a 4-(2-pyridylamidoethyl)piperidine of the structure ##EQU6## wherein R is selected from the group consisting of 3-(2-methoxy) pyridyl, 3-(2-ethoxy)pyridyl and 2-(4-chloro)pyridyl comprising contacting the corresponding 4-(2-pyridylamidoethyl)pyridine with a substantially equimolar portion of an agent chosen from the group consisting of benzyl bromide, benzyl iodide, the α-bromo- and α-iodoxylyenes, the α-bromo- and α-iodomethylnaphthalenes and the mono- and disubstituted derivaties thereof wherein said substituents are chosen from the group consisting of lower alkyl, lower alkoxy, phenyl and phenoxy, in reaction-inert solvent at reflux temperature until reaction to form the corresponding N-substituted-4-(2-pyridylamidoethyl)pyridinium salt is substantially complete; contacting said salt with metal hydride selected from the group consisting of sodium borohydride, lithium aluminum hydride and sodium bis-(2-methoxyethoxy)aluminum hydride in reaction-inert solvent until reaction to form the corresponding N-substituted-4-(2-pyridylamidoethyl)-1,2,5,6-tetrahydropyridine is substantially complete; and contacting said tetrahydropyridine with hydrogen at up to about 400 psig. from about 40° to 75°C. in reaction-inert solvent in the presence of moble metal catalyst and an approximately equimolar portion of acid until reaction to form the corresponding 4-(2-pyridylamidoethyl)piperidine is substantially complete.

Claim 11

The process of claim 8 wherein said agent is benzyl bromide.

Claim 12

The process of claim 9 wherein said agent is dissolved in acetonitrile.

Claim 13

The process of claim 8 wherein said metal hydride is sodium borohydride.

Claim 14

The process of claim 8 wherein said catalyst is palladium.

Claim 15

The process of claim 8 wherein contact with said metal hydride and hydrogen is effected in methanol.

Claim 16

The process of claim 11 wherein R is 3-(2-methoxy) pyridyl.